Plasma growth differentiation factor-15 is associated with cardiovascular events in patients hospitalized for acute exacerbation of COPD

Sep 30, 2026

Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) face heightened risk of major adverse cardiovascular events (MACE) and death. This analysis examined whether plasma biomarkers growth differentiation factor-15 (GDF-15) and Syndecan-1 predict a combined 5-year outcome of MACE or all-cause mortality. The sub-study involved 299 AECOPD patients from the randomized CORTICO-COP trial, with baseline biomarker levels measured in a biobank. Higher GDF-15 predicted increased risk of the combined endpoint and all-cause mortality, while Syndecan-1 showed no prognostic value.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Background

Cardiovascular risk in AECOPD

Study design

Embedded trial and participants

Biomarker measurement

Outcomes and results

Association with MACE or all-cause mortality

Discrimination and secondary outcomes

Conclusions

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Plasma growth differentiation factor-15 is associated with cardiovascular events in patients hospitalized for acute exacerbation of COPD Pradeesh Sivapalan1,2􀀍, Daniel Alexander Ackermann1, Anna Kubel Vognsen1, Ruth Frikke-Schmidt2,3, Jens P. Goetze3, Thérèse Lappere4,13, Christina Christoffersen3,5, Jon Torgny Wilcke1,2, Charlotte S. Ulrik2,6, Niklas Dyrby Johansen7, Mats C. Højbjerg Andersen7, Alexander G. Mathioudakis8,9, Jørgen Vestbo1,8, Manan Pareek10,11, Tor Biering-Sørensen7,10,11,12 & Jens-Ulrik Jensen1,2 Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are at increased risk of major adverse cardiovascular events (MACE) and death. Growth differentiation factor-15 (GDF-15), a marker of cellular stress and inflammation, and Syndecan-1, a marker of endothelial dysfunction, have been suggested as prognostic biomarkers in plasma for MACE. We aimed to assess their association with a combined outcome of MACE or all-cause mortality over a 5-year period. This sub-study was embedded within the randomized controlled trial CORTICOsteroid reduction in COPD (CORTICO-COP), which investigated the effects of eosinophil-guided corticosteroid therapy inpatients hospitalized with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) . A total of 299 patients hospitalized with AECOPD were included in this analysis. Baseline plasma concentrations of growth differentiation factor 15 (GDF-15) and Syndecan-1 were measured and stored in a biobank for later analysis. The primary outcome was MACE or all-cause mortality, secondary outcomes included heart failure, re-AECOPD, and all-cause mortality. Hazard ratios (HRs) between low and high biomarker levels were adjusted for age, smoking, sex, GOLD class, and kidney insufficiency. The area under the receiver operating curve (AUC) was reported for each model after 6 months and two years respectively. Among the 299 hospitalized AECOPD patients included in this sub-study of the randomized controlled trial CORTICOsteroid reduction in COPD (CORTICO-COP), higher baseline concentrations of GDF-15 were associated with an increased risk of the combined outcome of MACE or all-cause mortality (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.16–2.44, p = 0.007), as well as all-cause mortality alone (HR 1.5, 95% CI 1.07–2.19, p = 0.02) . GDF-15 showed moderate discriminative ability for survival, with anAUC of 64% at 6 months and 60% at 2 years. No significant associations [www. nature.com/scientificreports/](www. nature.com/scientificreports/) were observed between GDF-15 and heart failure or hospital re-admission due to respiratory disease. Syndecan-1 concentrations were not associated with the combined endpoint or any of the secondary outcomes. GDF-15 may identify AECOPD patients at risk of MACE and all-cause mortality. Syndecan-1 has no predictive value inAECOPD patients. Keywords Biomarker, COPD, AECOPD, Cardiovascular Risk, GDF-15, Syndecan-1 1Copenhagen Respiratory Research, Department of Medicine, Copenhagen University Hospital– Herlev and Gentofte, Copenhagen, Denmark. 2Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. 3Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark. 4Department of Respiratory Medicine, Antwerp University Hospital, 2650 Edegem, Belgium. 5Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3A, 2200 Copenhagen, Denmark. 6Department of Respiratory Medicine, Copenhagen University Hospital - Hvidovre, Hvidovre, Denmark. 7Department of Cardiology, Copenhagen University Hospital-Herlev and Gentofte, Gentofte, Denmark. 8Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Bio-Logical Science, The University of Manchester, Manchester Academic Health Science Centre, Manchester

FAQs

What clinical risk does the study focus on in AECOPD patients?

The study focuses on the risk of major adverse cardiovascular events (MACE) and death in patients hospitalized with acute exacerbation of COPD.

How were GDF-15 and Syndecan-1 assessed in this research?

Baseline plasma concentrations of GDF-15 and Syndecan-1 were measured and stored in a biobank for later analysis.

Which biomarker was associated with worse outcomes?

Higher baseline GDF-15 concentrations were associated with increased risk of MACE or all-cause mortality and with all-cause mortality alone, whereas Syndecan-1 was not associated with the combined endpoint or secondary outcomes.

Sep 30, 2026

Uploaded by Maya Linwood